The University of Sheffield
Department of Cardiovascular Science

Dr. Sheila Francis BSc PhD

Head of Department
Reader in Cardiovascular Science

Dr Sheila Francis

Address
Department of Cardiovascular Science
University of Sheffield
Medical School
Beech Hill Road
Sheffield S10 2RX
Tel: +44 (0)114 271 2233
Tel Secretary Victoria Palmer: +44 (0)114 226 1432
Fax: +44 (0)114 271 1863
Email: s.francis@sheffield.ac.uk

Biography:

I joined the University of Sheffield in 1990 after a BBSRC CASE PhD studentship at the University of Manchester. After 4 years as a Postdoctoral Research Associate in Cardiac Surgery (with Angelini) and Molecular Medicine (with Duff), I held an Independent Open Competition Fellowship from the Lloyd´s Tercentenary Foundation on the molecular and inflammatory basis of coronary artery disease. After being appointed Lecturer in 1994, I spent a sabbatical period in the Hynes Lab at MIT as a Fulbright Scholar. I am currently Reader in Cardiovascular Science at the University of Sheffield and Head of the Department of Cardiovascular Science.

Research Activities:

I have a long-standing interest in the role of interleukin-1 (IL-1) and its naturally occurring antagonist, IL-1ra in modulating vascular cell function in experimental models and in human disease. Over the past 10-15 years, I have shown that IL-1 and IL-1ra are increased in diseased human arteries and in other experimental cardiovascular systems. I described the association of a genetic variant of IL-1ra with coronary artery disease and showed that this variant alters protein levels and the biology of endothelial cells. Programme funding from the British Heart Foundation (with Professor David Crossman) allowed the use of strategies to inhibit IL-1 in several experimental models including atherosclerosis in mice. The impact of this early work alongside that of others has now been translated to man through the ILA-HEART and CANTOS trials. My current research areas of interest relate to the mechanisms by which IL-1 is released from endothelial cells, IL-1 related molecules and their antagonists, and the role of IL-1 in complex vascular phenotypes such as inflammatory vascular plaques in the brain and acute presentation of atherosclerosis after chronic infection. These studies are being undertaken in collaboration with colleagues in the Departments of Cardiovascular Science, Infection and Immunity and Chemistry at the University of Sheffield, the Universities of Manchester (Pinteaux, Allan, Rothwell), Leicester (Stover), the University of Virginia (Abbate) and others.

Teaching Interests:

I teach on the MSc in Molecular Medicine and lead doctoral and ACF development training modules on `How to present yourself and your data at conferences'.

I am committed to mentorship for postdoctoral researchers and Fellows. I lead the Postdoctoral Mentoring and Fellowship Coaching Programme for the Faculty and the Medical School Athena SWAN group.

Professional Activities:

Current Projects:

  1. Release of IL-1 from endothelial cells (Embassy of Libya).
  2. In-stent restenosis – are endothelial progenitor cells good or bad? (BHF (with Gunn)).
  3. Tribbles and Atherosclerosis (Fondation Leducq (with Kiss-Toth)).
  4. S.pneumoniae infection and atherosclerosis (MRC (with Dockrell)).
  5. Phosphate and atherosclerosis (BHF (with Chico)).
  6. Carbon monoxide releasing molecules (BHF (with Gunn/Iqbal, Motterlini and Mann)).
  7. TILRR in inflammation and vascular disease (BHF (with Qwarnstrom)).
  8. EMP2, inflammation and atherosclerosis (BHF (with Wilson)).

Selected Publications:

  1. Hameed AG, Arnold ND, Chamberlain JC, Pickworth JA, Paiva C, Dawson S, Cross S, Long L. Zhao L, Morrell NW, Crossman DC, Newman CM, Kiely DG, Francis SE, Lawrie A. Inhibition of TRAIL reverses experimental pulmonary hypertension. J Exp Med. 2012 209(11): 1919-1935.

  2. Denes A, Drake C, Stordy J, Chamberlain J, Mccoll BW, Gram H, Crossman D, Francis SE, Allan SM, Rothwell NJ. IL-1 mediates neuroinflammatory changes associated with diet-induced atherosclerosis. J Am Heart Assoc. 2012 1(3): e002006.

  3. Lawrie A, Hameed AG, Chamberlain JC, Arnold ND, Kennerley A, Hopkinson K, Pickworth J, Kiely DG, Crossman DC, Francis SE. Paigen diet-fed apoE knockout mice develop severe pulmonary hypertension in an IL-1 dependent manner. Am J Pathol. 2011 179(4): 1693-170

  4. Ellam T, Wilkie M, Chamberlain J, Crossman D, Eastell R, Francis S, Chico TJA. Dietary phosphate modulates atherogenesis and insulin resistance on ApoE knockout mice’. ATVB, 2011 31(9): 1988-1990.

  5. Chamberlain JC, Arnold ND, Lupton H, Crossman DC, Gunn J, Francis SE. In situ aortic stenting in mice. Cardiovasc. Res 2010; 85:38-44.

  6. Chamberlain JC, Francis SE, Brookes Z, Shaw G, Alp NJ, Graham D, Dower S, Crossman DC. IL-1 regulates multiple atherogenic pathways in response to fat feeding. PLoS ONE 2009;4(4):e5073.

  7. Evans D, Jackman L, Chamberlain J, Crosdale D, Judge H, Jetha K, Norman K, Francis S. Storey R. Platelet P2Y12R influences vessel wall response to arterial injury and thrombosis. Circulation 2009; 119:116-122.

  8. Chamberlain J, Dewberry RM, King AR, Dower SK, Crossman DC, Francis SE. IL1beta and signalling of IL-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice. Am J Pathol 2006; 168: 1396-403.

  9. Dewberry RM, Crossman DC, Francis SE. Interleukin-1 receptor antagonist (IL-1RN) genotype modulates the replicative capacity of human endothelial cells Circ Res 2003;92:1285.

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